In its progress from the basal layer (to which mitosis is normally restricted) toward the outer surface of the skin, the epidermal cell undergoes a programmed series of morphological changes which undoubtedly coincide with alterations in metabolic activities. Formation of the fibrils in the basal cell and the biogenesis of keratohyalin in the granular cell - combination of which appears to form the keratin fibers - must indicate the existence of specialized biochemical systems in these particular cells and must represent chemical steps in the differentiation of the epidermis. The etiologies of the basal cell tumor, the squamous cell carcinoma and psoriasis may involve aberrations in one or both of these biosynthetic processes. The overall objectives of this investigation are (a) to develop a detailed molecular description of the metabolic pathways, and the mechanisms of their control, for the biogenesis of the "tonofibril" protein in the basal and lower spinous cells and the "keratohyalin" protein in the granular cells and (b) to define the nature of the molecular lesions responsible for the pathology in psoriasis, squamous cell carcinoma, basal cell tumor and possibly other diseases of aberrant differentiation. Isolation of a "histidine-rich" protein, demonstration of its relationship to keratohyalin and study of aberrations in this interrelation in the above pathologies is an immediate goal of this effort.